An examination of multiple explanations for secondary hyperparathyroidism


Seven theories address the evolution of secondary hyperparathyroidism (SHPT) as chronic kidney disease (CKD) progresses. The tradeoff-in-the-nephron hypothesis states that the plasma parathyroid hormone ([PTH]) concentration rises because an increased phosphate concentration in the cortical distal nephron ([P]_CDN) reduces the ionized calcium concentration in that segment. In the present study, we compared this hypothesis to its predecessors.

We studied 30 patients with estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73m² (mean 29.5). To examine historic theories, we performed regressions of [PTH] on plasma concentrations of ionized calcium, phosphorus, 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, and fibroblast growth factor 23, and on calcium excreted per volume of filtrate (E_Ca/C_cr). To assess the tradeoff-in-the-nephron hypothesis, we examined regressions of [PTH] on 100/eGFR and phosphorus excreted per volume of filtrate (E_P/C_cr).

Regressions pertinent to historic theories yielded significant direct relationships between [PTH] and both E_Ca/C_cr and [FGF23], but neither association supported the theory to which it pertained. [PTH] varied directly with 100/eGFR and with E_P/C_cr, a surrogate for [P]_CDN. E_P/C_cr correlated strongly with 100/eGFR.

The only theory of SHPT that our data support is the tradeoff-in-the-nephron hypothesis. Other theories are not supported.